Viral Evasion of Host Immune System - SHOULD BE IN MICROBIOLOGY Flashcards
Give facts about viruses
Viruses - IC pathogens:
- Represented via. MHC I mechanisms
- Cellular immunity clears viral infection BUT is short-lived
- Internal viral proteins can be targets of cellular immunity as they vary LESS than surface antigens
- Evading viruse example inc. HSV
3 ways of Virus Evasion?
(1) Evasion of Antigen Loading to TAP
(2) Modulation of Tapasin Function & Prevention of MHC Transport
(3) Interfering with MHC Presentation at Cell Surface
Cellular I.R to viruses?
MHC Class I (present on ALL cells)
• presents ENDOGENOUS peptides
CD8+ T-cell will recognise MHC complex –> releases granzyme to kill cell
Explain the Virus Evasion technique of (1) Evasion of Antigen Loading to TAP
TAP = loads proteins onto MHC Class I
e.g. EBV, HSV & CMV
EBV - EBNA1 cannot be processed by the proteasome
HSV - ICP47 blocks access of processed peptide to TAP
CMV - US6 stops ATP binding to TAP thus preventing translocation
Explain the Virus Evasion technique of (2) Modulation of Tapasin Function & Prevention of MHC Transport
CMV
- US3 binds Tapasin and prevents peptides being loaded to MHC.
Adenovirus
- E3-19K prevents recruitment of TAP to Tapasin and retains MHC in ER.
Explain the Virus Evasion technique of (3) Interfering with MHC Presentation at Cell Surface
KSHV - Kaposi’s Sarcoma-associated Herpes Virus
KSHV
- kK3 protein induces polyubiquitinylation and internalisation of MHC.
o From internalised endosome, MHC is passed to lysosomes.
How do viruses evade the NK killing mechanism?
NK cells check that EVERY CELL has MHC Class I
• if does not, it is killed by NK cells
Viruses that disrupt MHC presentation would end up being killed by NK cells
Viruses therefore evade NK cells by:
• encoding its own MHC ANALOGUE
OR
• upregulate MHC
Why does Antigenic Variation occur?
o Continued rapid evolution driven by antigenic pressure from host
• influenza antigenic shift
• HIV quasispecies
o Introduction of new subtypes from animal sources
• influenza antigenic shift
o Existing as different stable serotypes that co-circulate in humans
• rhinovirus (100s)
• poliovirus (3)
• dengue (4)
o Consequence of vaccination
What is antigenic drift?
Change of ANTIGENS on a virus picked up from an infected cell that give it immunity to Abs formed against its old self
How does HIV avoid Abs?
HIV envelope spike gp120 resists neutralisation because:
Large space between spikes prevent Ab cross-linking.
Extensive glycosylation masks Ab epitopes.
Functionally important parts of antigen are poorly accessible – CD4 binding site.
What is the hope for treatment against HIV?
Antibodies that can cross-react with many HIV strains
• DOES exist alongside viruses in people that control infection
BNabs (Broadly Neutralising Abs) produced as biological therapies can control viral load
• this controls viral load but mutants do appear over time of used individually.
What does Dengue Virus cause and how can it be treated?
It causes leakage of blood plasma (fluid) from capillaries:
leads to an INCREASED haematocrit and RBC count and a DECREASED protein count in the blood
causes severe bruising and bleeding – patients deteriorate even after fever (due to shock).
Treat:
Treat with IV fluids.
Explain ADE of Dengue
Ab-Dependent Enhancement of Dengue
Dengue exists as 4 serotypes
Abs generated against a PREVIOUS infection can bind but NOT neutralise
this leads to ADE, causing a dengue haemorrhagic fever
This is as the dengue fever uses the Ab as an access into the monocyte where it reproduces!
Explain the poliovirus vaccine
• Polio – one serotype of polio has been completely eradicated, the vaccine is still a trivalent vaccine though.
o Live-attenuated Sabin vaccine – administration of all 3 at once resulted in virus interference and poor response to one component.
How can viruses evade the Ab response?
Glycoprotein antigens:
• these are so heavily glycosylated (mucin-like) that antibody access is hindered – e.g. HIV
Apoptotic body disguise
• Ebola virus particle membranes have a high phosphatidl serine lipid content
• this makes them look like apoptotic bodies so are taken up by micropinocytosis and hidden from the I.S
Viral filaments
• viral filaments are hard for Abs to neutralise as GLPs inaccessible in folded packets
How does Ebola evade the I.S?
Glycosylation of Antigens:
• due to heavy glycosylation, harder to neutralise (as in inaccessible folds)
Soluble Spike Proteins
• this mops up all the Abs SO that they bind to the soluble antigen rathen than the actual virus
• acts as Ab decoys (sGPs) - there are immunosuppresive & inhibit neutrophils
Act as Apoptotic Bodies
• so is taken up & hidden
What is the link between Measles and Immunosuppresion
Measles infects CD150+ cells, including MEMORY LYMPHOCYTES
• SO 2-3 years of immunological memory is lost
Therefore, following measles infection, can be re-infected with things that should be protected against
• hence why the vaccination lead to a much larger childhood mortality than expected (>90% reduction in death)
Universal Influenza Vaccine?
2 regions:
(1) Variable region (HA1) - mutates
(2) Conserved region (HA2) - remains constant
If we can make an Ab against the hemagglutinin 2 regions (the conserved region) then we could theoretically be immune against influenza as it’s just the variable region that mutates.
This would be another example of a Broadly Neutralising antibody (BNab).
Which answer is not true?
Viruses that can’t control the innate immune system well might….
A: be useful as oncolytic agents
B: be difficult to grow in standard cell culture systems
C: be restricted at crossing the host range barrier and unlikely to spark outbreaks in other species
D: be useful as live-attenuated vaccines
E: be highly adapted to their host species
E
Which is true?
Viruses counteract activation of the interferon system by:
A: varying their coat protein sequences
B: encoding proteins that cleave or target host factors for degradation
C: preventing the loading of peptides by TAP
D: inducing a cytokine storm
E: encoding MHC homologues
B
Which is true?
RNA viruses are more likely than DNA viruses to
A: code for proteins that interfere with innate immunity
B: code for proteins that interfere with cellular immunity
C: Have error prone polymerases that promote antigenic variation
D: Use lipid envelopes to protect their genomes that also contain host proteins that control complement activation
E: Activate interferon induction pathway through cGAS and STING.
C
Which is NOT true concerning the interplay between
Hepatitis C virus and the immune systems
A: Its E2 protein varies by more than 30% so antibodies only bind a tiny fraction of the viral quasispecies
B: T cell epitopes vary so that the virus is not cleared in the early stage of infection and this determines chronicity
C: NS3/4A protease cleaves MAVS and prevents activation of interferon
D: It encodes a protein called vif that counteracts the interferon stimulated gene APOBEC and prevent it from inducing hypermutation of the viral genome
E: A genetic polymorphism in IL28b results in non-responsivenes to interferon treatment
D - HIV does this
